Ic stage (two). Importantly, the differentiation induction therapy with all-trans retinoic acid

Ic stage (2). Importantly, the differentiation induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has strikingly improved the clinical outcome of classic APL sufferers. However, the PML ARA fusion gene is absent in 2Frontiers in Oncologyfrontiersin.orgZhao et al.ten.3389/fonc.2022.APL patients, which can be classified into variant APL or AML resembling APL (3). Among these, RARA rearrangement is reasonably typical with PLZF-RARA accounting for 50 variant APL. Retinoic acid receptor beta (RARB) and retinoic acid receptor gamma (RARG) rearrangements have also been demonstrated to generate AML resembling APL (4). The genetic heterogeneity, leukemogenesis mechanism, and optimal therapy regimen of these subtypes of AML remained to become elucidated, which pose a challenge to the recognition and treatment of variant APL. Herein, we identified a rare case of AML resembling APL together with the CPSF6RARG fusion gene who was resistant to ATRA and ATO but sensitive to homoharringtonine and cytarabine (HA) therapy.Case descriptionThe patient was a 28-year-old man with no substantial past medical history who presented with a 1-week history of petechiae. His blood count showed a white blood cell (WBC) count of 29.21 109/l, hemoglobin of 69 g/dl, along with a platelet count of 103 109/l. Fibrinogen and D-dimer levels were two.99 g/l and 44.22 mg/ml, respectively. PT and APTT had been 12 and 25.9 s, respectively. Bone marrow (BM) smear showed the hypercellularity with 41 predominantly abnormal hypergranular promyelocytes devoid of Auer rods (Figure 1A). Cytochemical staining revealed that the abnormal promyelocytes had powerful reactivity to myeloperoxidase (MPO). Flow cytometric immunophenotyping showed that the blasts were positive for CD13, CD33, CD117, CD38 (partial), and CD64 (partial) but damaging for HLA-DR, CD34, CD14, CD56, CD7, CD10, CD5, CD2, CD3, CD4, CD8, CD19, CD20, and CD138.MHP custom synthesis As a result, the diagnostic impression of APL was initially established. However, multiplex RT-qPCR showed that all of the myeloidrelated fusion transcripts had been negative, including PML-RARa,FIP1L1-RARa, PLZF-RARa, NPM-RARA, NUMA-RARa, STAT5RARa, and PRKAR1A-RARa. Fluorescence in situ hybridization also failed to detect the PML-RARA fusion gene (Figure 1B). Cytogenetic studies didn’t detect the translocation of t (15;17) (q24;q21) (Figure 1C). Whole-genome sequencing (WGS) identified K-RAS mutations in this patient. The patient was immediately treated with all-trans retinoic acid (ATRA), and arsenic trioxide (ATO) was started in addition to ATRA on day 2.α-Glucosidase site Immediately after 28 days of treatment, there have been still 39 abnormal promyelocytes in BM, indicating that the patient was resistant to ATRA and ATO.PMID:32926338 Then, one particular course of DA regimen (DNR 60 mg/m2, d1, Ara-C one hundred mg/m2, d1) was utilized as induction therapy. However, there was nonetheless no response. The patient received HA chemotherapy regimen (homoharringtonine four mg/day, d1, Ara-C one hundred mg/m2, d1) as reinduction therapy. The BM smear showed that the patient had accomplished total remission. Then, six courses of consolidation chemotherapy regimens were provided as follows: 2 cycles of decitabine + CAG regimen (decitabine 20 mg/m2, d1; aclarubicin 10 mg/m2, d3; Ara-C 10 mg/m2/q12h, d34; G-CSF 200 mg/day until WBC count was 20 109/l), two cycles on the HA regimen (homoharringtonine 4 mg/day, d1, Ara-C 100 mg/m2, d1), and 2 cycles in the middledose cytarabine (2 g/m2/q12h d1). As much as now, the patient remains alive and was leukemia-free at follow-up.